Saturday, 15 June 2019

A
KAIST research team developed a microfluidic-based drug screening chip that
identifies synergistic interactions between two antibiotics in eight hours.
This chip can be a cell-based drug screening platform for exploring critical
pharmacological patterns of antibiotic interactions, along with potential
applications in screening other cell-type agents and guidance for clinical
therapies.

Antibiotic
susceptibility testing, which determines types and doses of antibiotics that
can effectively inhibit bacterial growth, has become more critical in recent
years with the emergence of antibiotic-resistant pathogenic bacteria strains.

To
overcome the antibiotic-resistant bacteria, combinatory therapy using two or
more kinds of antibiotics has been gaining considerable attention. However, the
major problem is that this therapy is not always effective; occasionally,
unfavorable antibiotic pairs may worsen results, leading to suppressed
antimicrobial effects. Therefore, combinatory testing is a crucial preliminary
process to find suitable antibiotic pairs and their concentration range against
unknown pathogens, but the conventional testing methods are inconvenient for
concentration dilution and sample preparation, and they take more than 24 hours
to produce the results.

To reduce time and
enhance the efficiency of combinatory testing, Professor Jessie Sungyun Jeon
from the Department of Mechanical Engineering, in collaboration with Professor
Hyun Jung Chung from the Department of Biological Sciences, developed a
high-throughput drug screening chip that generates 121 pairwise concentrations
between two antibiotics.

The
team utilized a microfluidic chip with a sample volume of a few tens of
microliters. This chip enabled 121 pairwise concentrations of two antibiotics
to be automatically formed in only 35 minutes.

They
loaded a mixture of bacterial samples and agarose into the microchannel and
injected reagents with or without antibiotics into the surrounding
microchannel. The diffusion of antibiotic molecules from the channel with antibiotics
to the one without antibiotics resulted in the formation of two orthogonal
concentration gradients of the two antibiotics on the bacteria-trapping agarose
gel.

The
team observed the inhibition of bacterial growth by the antibiotic orthogonal gradients
over six hours with a microscope, and confirmed different patterns of
antibiotic pairs, classifying the interaction types into either synergy or
antagonism.

Professor
Jeon said, "The feasibility of microfluidic-based drug screening chips is
promising, and we expect our microfluidic chip to be commercialized and
utilized in near future."